Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis. Issue 2 (22nd February 2022)

• Record Type: Journal Article
• Authors: Li, Siming; Wu, Xiaowen; Yan, Xieqiao; Zhou, Li; Chi, Zhihong; Si, Lu; Cui, Chuanliang; Tang, Bixia; Mao, Lili; Lian, Bin; Wang, Xuan; Bai, Xue; Dai, Jie; Kong, Yan; Tang, Xiongwen; Feng, Hui; Yao, Sheng; Flaherty, Keith T; Guo, Jun; Sheng, Xinan
• Is Part Of: Journal for immunotherapy of cancer. Volume 10:Issue 2(2022)
• Publication Date: 2022-02-22
• Subjects: melanoma -- immunotherapy -- drug therapy -- combination -- biomarkers -- tumor; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2021-004036
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Mucosal melanoma is an aggressive melanoma subtype with poor response to antiprogrammed cell death-1 (PD-1) monotherapy. Axitinib in combination with toripalimab, a humanized IgG4 mAb against PD-1, showed a promising response rate in patients with metastatic mucosal melanoma (MM) in a phase Ib study. Here, we report the updated overall survival (OS), duration of response (DoR), and biomarker analysis results. Methods: Patients with advanced MM received toripalimab 1 or 3 mg/kg intravenously every 2 weeks combined with axitinib 5 mg orally two times per day until disease progression or unacceptable toxicity. Tumor programmed cell death ligand-1 (PD-L1) expression, tumor mutational burden (TMB), and gene expression profile (GEP) by messenger RNA sequencing were evaluated for correlation with survival. Results: As of April 2, 2021, the median follow-up was 42.5 months. Among 29 chemotherapy-naïve patients with metastatic MM, the median OS was 20.7 months (95% CI 9.7 to 32.7 months); the median progression-free survival (PFS) was 7.5 months (95% CI 3.8 to 14.8 months); and the median DoR was 13.4 months (95% CI 5.5 to 20.6 months). The OS rates of 1, 2, and 3 years were 62.1%, 44.8%, and 31.0%, respectively. Biomarker analysis found that PD-L1 expression and TMB level were not associated with survival benefits. In contrast, a 12-GEP signature correlated with improved PFS (17.7 vs 5.7 months, p=0.0083) and OS (35.6 vs 17.6 months, p=0.039). Conclusions: The 3-year survival update confirmed the antitumor activity and long-term survival benefit of the toripalimab plus axitinib combination in patients with advanced MM. The 12-gene GEP is of value in predicting the outcomes of vascular endothelial growth factor receptor-tyrosine kinase inhibitor and PD-1 blockade combination therapy, but requires further validation. Trial registration numbers: NCT03086174 .